JBM  Vol.5 No.3 , March 2017
What Does GABAergic Neurotransmission System Do in Acupuncture Analgesia?
Abstract: As one of the essential components of traditional Chinese medicine, acupuncture has been accepted world-widely for its effectiveness in treating various disease and health conditions. Pain management is one of the least controversial therapeutic benefits of acupuncture treatment. To date, the mechanism underlying acupuncture analgesia remains poorly understood. In this review, roles of members of GABAergic neurotransmission system which has long been related to pain perception and modulation, in acupuncture analgesia are discussed.
Cite this paper: Xu, Y. (2017) What Does GABAergic Neurotransmission System Do in Acupuncture Analgesia?. Journal of Biosciences and Medicines, 5, 61-70. doi: 10.4236/jbm.2017.53007.

[1]   Xia, Y., Ding, G. and Wu, G.C. (2012) Current Research in Acupuncture. Springer, New York.

[2]   Eisenberg, D.M., Kessler, R.C., Foster, C., Norlock, F.E., Calkins, D.R. and Delbanco, T.L. (1993) Unconventional Medicine in the United States. Prevalence, Costs, and Patterns of Use. The New England Journal of Medicine, 328, 246-252.

[3]   Cherkin, D.C., Deyo, R.A., Sherman, K.J., Hart, L.G., Street, J.H., Hrbek, A., Davis, R.B., Cramer, E., Milliman, B., Booker, J., Mootz, R., Barassi, J., Kahn, J.R., Kaptchuk, T.J. and Eisenberg, D.M. (2002) Characteristics of Visits to Licensed Acupuncturists, Chiropractors, Massage Therapists, and Naturopathic Physicians. The Journal of the American Board of Family Practice, 15, 463-472.

[4]   Kaptchuk, T.J. (2002) Acupuncture: Theory, Efficacy, and Practice. Annals of Internal Medicine, 136, 374-383.

[5]   Berman, B.M., Langevin, H.M., Witt, C.M. and Dubner, R. (2010) Acupuncture for Chronic Low Back Pain. The New England Journal of Medicine, 363, 454-461.

[6]   Vickers, A.J., Cronin, A.M., Maschino, A.C., Lewith, G., MacPherson, H., Foster, N.E., Sherman, K.J., Witt, C.M. and Linde, K. (2012) Acupuncture for Chronic Pain: Individual Patient Data Meta-Analysis. Archives of Internal Medicine, 172, 1444-1453.

[7]   Shengelia, R., Parker, S.J., Ballin, M., George, T. and Reid, M.C. (2013) Complementary Therapies for Osteoarthritis: Are They Effective? Pain Management Nursing, 14, e274-e288.

[8]   Wong Lit, W.D., Wang, Y., Xue, C.C., Wang, L.P., Liang, F.R. and Zheng, Z. (2015) Local and Distant Acupuncture Points Stimulation for Chronic Musculoskeletal Pain: A Systematic Review on the Comparative Effects. European Journal of Pain, 19, 1232-1247.

[9]   Cheong, K.B., Zhang, J.P., Huang, Y. and Zhang, Z.J. (2013) The Effectiveness of Acupuncture in Prevention and Treatment of Postoperative Nausea and Vomiting—A Systematic Review and Meta-Analysis. PLoS ONE, 8, e82474.

[10]   Sawynok, J. (1984) GABAergic Mechanisms in Antinociception. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 8, 581-586.

[11]   Fundytus, M.E. (2001) Glutamate Receptors and Nociception: Implications for the Drug Treatment of Pain. CNS Drugs, 15, 29-58.

[12]   Zhou, H.Y., Zhang, H.M., Chen, S.R. and Pan, H.L. (2007) Increased Nociceptive Input Rapidly Modulates Spinal GABAergic Transmission through Endogenously Released Glutamate. Journal of Neurophysiology, 97, 871-882.

[13]   Schwarz, W. and Gu, Q. (2013) Cellular Mechanisms in Acupuncture Points and Affected Sites. In: Xia, Y., Ding, G. and Wu, G., Eds., Current Research in Acupuncture, Springer, New York, 37-51.

[14]   Liang, J. and Xia, Y. (2012) Acupuncture Modulation of Neutral Transmitters/ Modulators. In: Xia, Y., Ding, G. and Wu, G., Eds., Current Research in Acupuncture, Springer, New York, 1-36.

[15]   Hesse, T., Henkel, B., Zygmunt, M., Mustea, A. and Usichenko, T.I. (2016) Acupuncture for Pain Control after Caesarean Section: A Prospective Observational Pilot Study. Acupuncture in Medicine, 34, 14-19.

[16]   Melzack, R. and Wall, P.D. (1965) Pain Mechanisms: A New Theory. Science, 150, 971-979.

[17]   Enna, S.J. and McCarson, K.E. (2006) The Role of GABA in the Mediation and Perception of Pain. Advances in Pharmacology, 54, 1-27.

[18]   Jasmin, L., Wu, M.V. and Ohara, P.T. (2004) GABA Puts a Stop to Pain. Current Drug Target-CNS & Neurological Disorders, 3, 487-505.

[19]   Eaton, M.J., Martinez, M.A. and Karmally, S. (1999) A Single Intrathecal Injection of GABA Permanently Reverses Neuropathic Pain after Nerve Injury. Brain Research, 835, 334-339.

[20]   Lorenzo, L.E., Godin, A.G., Wang, F., St-Louis, M., Carbonetto, S., Wiseman, P.W., Ribeiro-da-Silva, A. and De, K.Y. (2014) Gephyrin Clusters Are Absent from Small Diameter Primary Afferent Terminals Despite the Presence of GABAA Receptors. Journal of Neuroscience, 34, 8300-8317.

[21]   Paul, J., Zeilhofer, H.U. and Fritschy, J.M. (2012) Selective Distribution of GABAA Receptor Subtypes in Mouse Spinal Dorsal Horn Neurons and Primary Afferents. Journal of Comparative Neurology, 520, 3895-3911.

[22]   Witschi, R., Punnakkal, P., Paul, J., Walczak, J.S., Cervero, F., Fritschy, J.M., Kuner, R., Keist, R., Rudolph, U. and Zeilhofer, H.U. (2011) Presynaptic α2-GABAA Receptors in Primary Afferent Depolarization and Spinal Pain Control. Journal of Neuroscience, 31, 8134-8142.

[23]   Malan, T.P., Mata, H.P. and Porreca, F. (2002) Spinal GABAA and GABAB Receptor Pharmacology in a Rat Model of Neuropathic Pain. Anesthesiology, 96, 1161-1167.

[24]   Gwak, Y.S., Tan, H.Y., Nam, T.S., Paik, K.S., Hulsebosch, C.E. and Leem, J.W. (2006) Activation of Spinal GABA Receptors Attenuates Chronic Central Neuropathic Pain after Spinal Cord Injury. Journal of Neurotrauma, 23, 1111-1124.

[25]   Hu, J.H., Yang, N., Ma, Y.H., Zhou, X.G., Jiang, J., Duan, S.H., Mei, Z.T., Fei, J. and Guo, L.H. (2003) Hyperalgesic Effects of Gamma-Aminobutyric Acid Transporter I in Mice. Journal of Neuroscience Research, 73, 565-572.

[26]   Xu, Y.F., Cai, Y.Q., Cai, G.Q., Jiang, J., Sheng, Z.J., Wang, Z.G. and Fei, J. (2008) Hypoalgesia in Mice Lacking GABA Transporter Subtype 1. Journal of Neuroscience Research, 86, 465-470.

[27]   Gao, M., Li, Q., Zhang, J. and Liu, Y. (1990) Effect of Changing the Functional State of Frontal Cortex by GABA on the Acupuncture Effect of PAG Neurons. Acupuncture Research, 15, 264-268.

[28]   Yan, L.P., Wu, X.T., Yin, Z.Y. and Ma, C. (2011) Effect of Electroacupuncture on the Levels of Amino Acid Neurotransmitters in the Spinal Cord in Rats with Chronic Constrictive Injury. Acupuncture Research, 36, 353-356, 379.

[29]   Sigel, E. and Steinmann, M.E. (2012) Structure, Function, and Modulation of GABAA Receptors. The Journal of Biological Chemistry, 287, 40224-40231.

[30]   Schwenk, J., Metz, M., Zolles, G., Turecek, R., Fritzius, T., Bildl, W., Tarusawa, E., Kulik, A., Unger, A., Ivankova, K., Seddik, R., Tiao, J.Y., Rajalu, M., Trojanova, J., Rohde, V., Gassmann, M., Schulte, U., Fakler, B. and Bettler, B. (2010) Native GABAB Receptors Are Heteromultimers with a Family of Auxiliary Subunits. Nature, 465, 231-235.

[31]   Foster, J.D., Kitchen, I., Bettler, B. and Chen, Y. (2013) GABAB Receptor Subtypes Differentially Modulate Synaptic Inhibition in the Dentate Gyrus to Enhance Granule Cell Output. British Journal of Pharmacology, 168, 1808-1819.

[32]   Heaney, C.F. and Kinney, J.W. (2016) Role of GABAB Receptors in Learning and Memory and Neurological Disorders. Neuroscience & Biobehavioral Reviews, 63, 1-28.

[33]   Gao, Y.H., Chen, S.P., Wang, J.Y., Qiao, L.N., Han, Y.J., Lin, D., Ji, C.F., Xu, Q.L. and Liu, J.L. (2012) Effects of Electroacupuncture of “Futu” (LI 18), etc. on Pain Behavior and Expression of GABA Receptor Subunit Genes in Cervical Spinal Cord in Rats with Thyroid Regional Pain. Acupuncture Research, 37, 93-98.

[34]   Li, C., Zhu, L., Li, W. and Ji, C. (1993) Relationship between the Presynaptic Depolarization Effect of Acupuncture and r-Aminobutyric Acid, Opioid Peptide and Substance P. Acupuncture Research, 18, 178-182.

[35]   Silva, J.R., Silva, M.L. and Prado, W.A. (2011) Analgesia Induced by 2- or 100-Hz Electroacupuncture in the Rat Tail-Flick Test Depends on the Activation of Different Descending Pain Inhibitory Mechanisms. The Journal of Pain, 12, 51-60.

[36]   Silva, M.L., Silva, J.R. and Prado, W.A. (2013) Analgesia Induced by 2- or 100-Hz Electroacupuncture in the Rat Tail-Flick Test Depends on the Anterior Pretectal Nucleus. Life Sciences, 93, 742-754.

[37]   Rees, H. and Roberts, M.H. (1993) The Anterior Pretectal Nucleus: A Proposed Role in Sensory Processing. Pain, 53, 121-135.

[38]   Chakrabarti, S. and Poddar, M.K. (1989) Effect of Diazepam on Electroacupuncture-Induced Changes in Regional Gamma-Aminobutyric Acid of the Rat Central Nervous System. Neuroscience Research, 7, 24-32.

[39]   Rudolph, U., Crestani, F., Benke, D., Brunig, I., Benson, J.A., Fritschy, J.M., Martin, J.R., Bluethmann, H. and Mohler, H. (1999) Benzodiazepine Actions Mediated by Specific Gamma-Aminobutyric AcidA Receptor Subtypes. Nature, 401, 796-800.

[40]   Liu, Q.R., Lopez-Corcuera, B., Mandiyan, S., Nelson, H. and Nelson, N (1993) Molecular Characterization of Four Pharmacologically Distinct Gamma-Aminobutyric Acid Transporters In Mouse Brain [Corrected]. The Journal of Biological Chemistry, 268, 2106-2112.

[41]   Lopez-Corcuera, B., Liu, Q.R., Mandiyan, S., Nelson, H. and Nelson, N. (1992) Expression of a Mouse Brain cDNA Encoding Novel Gamma-Aminobutyric Acid Transporter. The Journal of Biological Chemistry, 267, 17491-17493.

[42]   Radian, R., Bendahan, A. and Kanner, B.I. (1986) Purification and Identification of the Functional Sodium- and Chloride-Coupled Gamma-Aminobutyric Acid Transport Glycoprotein from Rat Brain. The Journal of Biological Chemistry, 261, 15437-15441.

[43]   Borden, L.A., Smith, K.E., Hartig, P.R., Branchek, T.A. and Weinshank, R.L. (1992) Molecular Heterogeneity of the Gamma-Aminobutyric Acid (GABA) Transport System. Cloning of Two Novel High Affinity GABA Transporters from Rat Brain. The Journal of Biological Chemistry, 267, 21098-21104.

[44]   Borden, L.A., Dhar, T.G., Smith, K.E., Branchek, T.A., Gluchowski, C. and Weinshank, R.L. (1994) Cloning of the Human Homologue of the GABA Transporter GAT-3 and Identification of a Novel Inhibitor with Selectivity for This Site. Receptors and Channels, 2, 207-213.

[45]   Borden, L.A., Smith, K.E., Gustafson, E.L., Branchek, T.A. and Weinshank, R.L. (1995) Cloning and Expression of a Betaine/GABA Transporter from Human Brain. Journal of Neurochemistry, 64, 977-984.

[46]   Jensen, K., Chiu, C.S., Sokolova, I., Lester, H.A. and Mody, I. (2003) GABA Transporter-1 (GAT1)-Deficient Mice: Differential Tonic Activation of GABAA versus GABAB Receptors in the Hippocampus. Journal of Neurophysiology, 90, 2690-2701.

[47]   Mayer, D.J., Price, D.D. and Rafii, A. (1977) Antagonism of Acupuncture Analgesia in Man by the Narcotic Antagonist Naloxone. Brain Research, 121, 368-372.

[48]   Pomeranz, B. and Chiu, D. (1976) Naloxone Blockade of Acupuncture Analgesia: Endorphin Implicated. Life Sciences, 19, 1757-1762.

[49]   Cheng, R.S. and Pomeranz, B. (1979) Electroacupuncture Analgesia Could Be Mediated by at Least Two Pain-Relieving Mechanisms; Endorphin and Non-Endorphin Systems. Life Sciences, 25, 1957-1962.

[50]   Han, J.S. (2004) Acupuncture and Endorphins. Neuroscience Letters, 361, 258-261.

[51]   Pu, L., Xu, N., Xia, P., Gu, Q., Ren, S., Fucke, T., Pei, G. and Schwarz, W. (2012) Inhibition of Activity of GABA Transporter GAT1 by Delta-Opioid Receptor. Evidence-Based Complementary and Alternative Medicine, 2012, Article ID: 818451.

[52]   Pu, L., Xu, Y. and Schwarz, W. (2015) Regulation of Membrane Transporters by Delta-Opioid Receptors. In: Xia, Y., Ed., Neural Function of the Delta-Opioid Receptor, Springer, Berlin, 349-362.